Fibrillar structures and plaques, stemming from aggregation of amyloid � (A�) peptides, are found in the brains of those suffering from Alzheimer's disease (AD). There is an incomplete understanding of the role of A� aggregate structure in AD, as the concentration of fibrillar plaques has not been shown to correlate directly with the severity of the disease. It has been suggested that A� oligomers, which form through an alternate aggregation pathway, may play a greater role in neuronal degeneration than that of fibrils. We have previously demonstrated changes in the A� aggregation pathway as a function of structure and concentration of fatty acids in model studies (in vitro). It has been shown by others that interaction with various modulators, such as phosphatidylserine and GM1 gangliosides, induces A� peptide aggregation and conformational change into toxic species. The impact of structure and concentration of GM1 gangliosides, which increase in concentration in neuronal cells with increasing age, has not yet been reported. We have created synthetic polymer models with substituent groups that mimic the saccharide head group of GM1 gangliosides, through the use of aqueous RAFT polymerization, to investigate systematically the effect of the components and concentration of the modulator on A� aggregation pathway. A series of homopolymers and statistical copolymers, derived from monomers dimethylacrylamide (DMA), hydroxyethylacrylamide (HEAm), 2-(�-D-glucosyloxy)ethyl acrylamide [GlcEAm] and 2-(�-D-galactosyloxy)ethyl acrylamide [GalEAm], were synthesized. These polymers were characterized through 1H NMR, ASEC-MALLS and SLS, and utilized to evaluate the conformational change and aggregation of A�.

Synthesis of statistical copolymers of dimethylacrylamide (DMA) with hydroxyethylacrylamide (HEAm), 2-(�-D-galactosyloxy)ethyl acrylamide (GalEAm) and 2-(�-D-glucosyloxy)ethyl acrylamide (GlcEAm) for systematic evaluation of the aggregation of amyloid � peptides

248th National Meeting (2014)

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